Early life, education, and early career
Selsam's education began in public schools in the Harrisburg area. Later, Selsam received his undergraduate degree in 1924 from Franklin & Marshall College, Lancaster, Pennsylvania. From 1924 through 1927, he taught at the American University of Beirut. Later, Selsam did graduate work in philosophy at Columbia University. At Columbia, he received both his MA (1928)  and PhD (1931). Selsam's master's thesis dealt with Baron d'Holbach,  and his dissertation concerned the English Hegelian philosopher Thomas Hill Green.
After receiving his PhD, Selsam served as an instructor and later as an assistant professor at Brooklyn College. Active politically, Selsam participated in anti-war events on campus   and took "an active part in the social struggles of his day on the side of the communist movement." Selsam's involvement is echoed in a contemporary newspaper article where Selsam is associated with Communist Party USA activities,   yet he was careful not to impose his political beliefs on students.  The political activities of Selsam and other Brooklyn College faculty members attracted the attention of governmental investigation. Despite their denials of Communist association to reporters,  Selsam and other faculty members later lost their teaching positions due to the Rapp-Coudert Committee investigations into Communist involvement in public education in New York State.  That Selsam refused to testify at the hearings and faced contempt charges  likely made his resignation unavoidable. 
School for Democracy and Jefferson School of Social Science
Selsam served as the director of the Jefferson School of Social Science, which was a "Marxist adult education facility"  whose faculty included "leftist academics dismissed from the City University of New York."  He held this position from 1944-1956. 
During Selsam's period of leadership, there was a steady flow of students at the Jefferson School. Even during the hey-day of Senator Joseph McCarthy's well publicized investigations into Communist subversion, the Jefferson School had an enrollment of 5,000 students each term.  Nevertheless, the school received criticism claiming that students simply received dogmatic instruction. For example, a Rutgers University economics professor, Alexander Balinky enrolled in the school and took some classes. Based on his experiences at the school, Balinky wrote a newspaper article and claimed that the students received political indoctrination at the school. 
Due to tensions caused by the Cold War, Anti-communism, and McCarthyism, the Jefferson School was subject to Congressional hearings and Selsam and others received summons to testify on several occasions.  For example, Selsam testified before the U.S. Senate's Internal Security Subcommittee on 8 April 1953, and, during Selsam's testimony, he often invoked the Fifth Amendment. 
Selsam and other school administrators denied that the school was a Communist front and fought against having it so officially labeled.  Given the political radicalism of the faculty members and the Marxist-oriented instruction at the school, and facing external political pressure against the school, declining student enrollment, and publication in the West of Nikita Khrushchev's secret speech —a speech which described in detail Stalin's crimes and political purges —all of these factors ultimately forced the school administrators to close down the school in 1956. 
Khrushchev's secret speech and its aftermath caused considerable turmoil within the Communist Party USA, and Selsam and other Jefferson School faculty members openly quit the Party in a joint letter published in the May 6, 1956 issue of the Daily Worker. 
Later years and death
With the closure of the Jefferson School of Social Science, Selsam devoted much of his time lecturing and writing. He wrote a number of books on Marxist topics for International Publishers. Many of these books were republished in Canada, England, and India. In addition, Selsam's books were translated into a variety of languages, including Spanish, Arabic, Polish, Russian, German, Hungarian, and Japanese.
Besides writing books, Selsam wrote articles and reviews for periodicals, including The New Masses, and Marxism Today. He worked closely and collaborated with his wife Millicent Selsam, a botanist and high school teacher  who was well known as an author of science books for young people.
Besides writing for the The New Masses and Marxism Today, Selsam was an editorial board member for the Marxist journal Science & Society,   and he was a founder of the American Institute for Marxist Studies.